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Pulmonary tuberculosis (PTB), remains one of the leading causes of death from infectious diseases worldwide, its burden is disproportionately affecting low- and middle-income countries (LMICs), including Tanzania. This study aimed to examine the direct and indirect costs incurred by patients and their families prior to PTB diagnosis, and how such costs influence patients' health-seeking behaviours. A mixed-methods approach was employed, integrating qualitative and quantitative methods for data collection, analysis, and interpretation. The study was part of a longitudinal observational cohort that included 261 adults diagnosed with PTB. Quantitative data were collected using a structured questionnaire adapted from the WHO's generic patient cost survey tool, administered after TB diagnosis was confirmed. To gain deeper insights, additional data were gathered through, in-depth interviews (IDIs) with purposively selected participants, aimed at identifying both financial and non-financial challenges experienced by patients and their family supporters before to diagnosis. Of the 261 respondents, 59% were men, 48% were married, and 51% were living with HIV, with a median age of 35 years. The majority 185(72.8%) delaying visiting a healthcare facility (HCF) by more than four weeks following the onset of symptoms. The average total pre-treatment cost per patient was USD 28.8, comprising direct medical, direct non-medical, and indirect costs. These costs varied based on the number and type of healthcare providers consulted. Qualitative findings indicated that participants frequently associated this pre-treatment costs with delays in seeking formal care, often influenced by self-medication, limited awareness of TB symptoms, and long distances to formal HCFs. This study highlights the significant financial and non-financial barriers faces by patients diagnosed with PTB and their families before diagnosis. Delays in care-seeking not only worsen health outcomes but also increase the overall economic burden. Addressing these challenges requires a comprehensive, multisectoral approach to improve early diagnosis, reduce patients costs and strengthen TB control efforts in high-burden settings.

Childhood tuberculosis remains a major cause of morbidity and mortality in part due to missed diagnosis. Diagnostic methods with enhanced sensitivity using easy-to-obtain specimens are needed. We aimed to assess the diagnostic accuracy of the Cepheid Mycobacterium tuberculosis Host Response prototype cartridge (MTB-HR), a candidate test measuring a three-gene transcriptomic signature from fingerstick blood, in children with presumptive tuberculosis disease. RaPaed-TB was a prospective diagnostic accuracy study conducted at four sites in African countries (Malawi, Mozambique, South Africa, and Tanzania) and one site in India. Children younger than 15 years with presumptive pulmonary or extrapulmonary tuberculosis were enrolled between Jan 21, 2019, and June 30, 2021. MTB-HR was performed at baseline and at 1 month in all children and was repeated at 3 months and 6 months in children on tuberculosis treatment. Accuracy was compared with tuberculosis status based on standardised microbiological, radiological, and clinical data. 5313 potentially eligible children were screened, of whom 975 were eligible. 784 children had MTB-HR test results, of whom 639 had a diagnostic classification and were included in the analysis. MTB-HR differentiated children with culture-confirmed tuberculosis from those with unlikely tuberculosis with a sensitivity of 59·8% (95% CI 50·8–68·4). Using any microbiological confirmation (culture, Xpert MTB/RIF Ultra, or both), sensitivity was 41·6% (34·7–48·7), and using a composite clinical reference standard, sensitivity was 29·6% (25·4–34·2). Specificity for all three reference standards was 90·3% (95% CI 85·5–94·0). Performance was similar in different age groups and by malnutrition status. Among children living with HIV, accuracy against the strict reference standard tended to be lower (sensitivity 50·0%, 15·7–84·3) compared with those without HIV (61·0%, 51·6–69·9), although the difference did not reach statistical significance. Combining baseline MTB-HR result with one Ultra result identified 71·2% of children with microbiologically confirmed tuberculosis. MTB-HR showed promising diagnostic accuracy for culture-confirmed tuberculosis in this large, geographically diverse, paediatric cohort and hard-to-diagnose subgroups. European and Developing Countries Clinical Trials Partnership, UK Medical Research Council, Swedish International Development Cooperation Agency, Bundesministerium für Bildung und Forschung; German Center for Infection Research (DZIF).

This study showed the diversity of circulating HPV genotypes in Togo. Programs of HPV vaccination and early detection of benign or precancerous lesions should be implemented to reduce cancer-related comorbidities.

A sensitive and specific non-sputum-based test would be groundbreaking for the diagnosis of childhood tuberculosis. We assessed side by side the diagnostic accuracy of the urine-based lipoarabinomannan assays Fujifilm SILVAMP TB LAM (FujiLAM) and Alere Determine TB LAM Ag (AlereLAM) for detection of childhood tuberculosis. In this cross-sectional study, we tested urine samples from children younger than 15 years with presumed pulmonary tuberculosis. Children were consecutively recruited from four dedicated outpatient childhood tuberculosis clinics in The Gambia, Mali, Nigeria, and Tanzania. Biobanked urine samples were thawed and tested using FujiLAM and AlereLAM assays. We measured diagnostic performance against a microbiological reference standard (confirmed tuberculosis) and a composite reference standard (confirmed and unconfirmed tuberculosis). Sensitivity and specificity were estimated with bivariate random-effects meta-analyses. Between July 1, 2017, and Dec 1, 2018, we obtained and stored urine samples from 415 children. 63 (15%) children had confirmed tuberculosis, 113 (27%) had unconfirmed tuberculosis, and 239 (58%) were unlikely to have tuberculosis. 61 children were HIV-positive (prevalence 15%). Using the microbiological reference standard, the sensitivity of FujiLAM was 64·9% (95% CI 43·7–85·2; positive in 40 of 63 confirmed samples) and the sensitivity of AlereLAM was 30·7% (8·6–61·6; 19 of 63). The specificity of FujiLAM was 83·8% (95% CI 76·5–89·4; negative in 297 of 352 unconfirmed and unlikely samples) and the specificity of AlereLAM was 87·8% (79·0–93·7; 312 of 352). Against the composite reference standard, both assays had decreased sensitivity; the sensitivity of FujiLAM was 32·9% (95% CI 24·6–41·9; positive in 58 of 176 confirmed and unconfirmed samples) and the sensitivity of AlereLAM was 20·2% (12·3–29·4; 36 of 176). The specificity of FujiLAM was 83·3% (95% CI 71·8–91·7; negative in 202 of 239 unlikely samples) and the specificity of AlereLAM was 90·0% (81·6–95·6; 216 of 239). By comparison with AlereLAM, FujiLAM showed higher sensitivity and similar specificity. FujiLAM could potentially add value to the rapid diagnosis of tuberculosis in children. German Federal Ministry of Education and Research, the Global Health Innovative Technology Fund, the UK Research and Innovation Global Challenges Research Fund, and the UK Medical Research Council.

Tuberculosis infection (TBI) testing, and treatment are fundamental to achieve TB elimination. TBI testing among close or household contacts (HHCs) has been limited, in part due to perceived complexity and high operational cost. We evaluated the performance of a new near-patient and field-based QIAreach QuantiFERON-TB (QIAreach) against QuantiFERON-TB-Gold-Plus (QFT-Plus) among HHCs of people with TB. A cross-sectional study was conducted from July 2021 to September 2022 in Lesotho, South Africa and Tanzania. Blood samples were collected from HHCs for paired QFT-Plus and QIAreach processing, testing and interpretation. To evaluate the performance of QIAreach against QFT-Plus as a reference, we determined the: i) prevalence of TBI, ii) total concordance using Cohen's Kappa, iii) predictors of discordant results using logistic regression, and iv) relationship between time to results and interferon-gamma (IFN-γ) response levels using linear correlation. Out of 964 enrolled HHCs, 464 had paired results, of whom 64.9% (302/465) were female with a cohort median age of 27 years (interquartile range (IQR): 13-45). Overall, 50.9% (236/464) tested positive on QFT-Plus, while 57.1% (265/464) were positive on QIAreach assay. Total concordance between QFT-Plus and QIAreach was 78.4% [353/450, 95% confidence interval (CI): 74.4-82.2, Cohen's Kappa: 0.5627, p < 0.001]. Discordance between assays was 23.9% (111/464) and was associated with Lesotho site (adjusted odds ratio 2.70, 95%CI: 1.48-4.92, p = 0.001). HHCs with higher IFN-γ response (QFT-Plus) (≥0.35 IU.ml-l) had a shorter time to results on QIAreach. In addition, a strong negative correlation between QIAreach time to results and IFN-γ response (QFT-Plus) levels (R = -0.64, 95% CI: -0.87 to -0.41, p < 0.001) was observed. QIAreach demonstrated a moderate concordance against QFT-Plus among HHCs in three high-burden countries. Further work is needed to understand and improve its usability in high TB and low resource settings.

Despite causing high mortality worldwide, paediatric tuberculosis is often undiagnosed. We aimed to investigate optimal testing strategies for microbiological confirmation of tuberculosis in children younger than 15 years, including the yield in high-risk subgroups (eg, children younger than 5 years, with HIV, or with severe acute malnutrition [SAM]). For this secondary analysis, we used data from RaPaed-TB, a multicentre diagnostic accuracy study evaluating novel diagnostic assays and testing approaches for tuberculosis in children recruited from five health-care centres in Malawi, Mozambique, South Africa, Tanzania, and India conducted between Jan 21, 2019, and June 30, 2021. Children were included if they were younger than 15 years and had signs or symptoms of pulmonary or extrapulmonary tuberculosis; they were excluded if they weighed less than 2 kg, had received three or more doses of anti-tuberculosis medication at time of enrolment, were in a condition deemed critical by the local investigator, or if they did not have at least one valid microbiological result. We collected tuberculosis-reference specimens via spontaneous sputum, induced sputum, gastric aspirate, and nasopharyngeal aspirates. Microbiological tests were Xpert MTB/RIF Ultra (hereafter referred to as Ultra), liquid culture, and Löwenstein–Jensen solid culture, which were followed by confirmatory testing for positive cultures. The main outcome of this secondary analysis was categorising children as having confirmed tuberculosis if culture or Ultra positive on any sample, unconfirmed tuberculosis if clinically diagnosed, and unlikely tuberculosis if neither of these applied. Of 5313 children screened, 975 were enrolled, of whom 965 (99%) had at least one valid microbiological result. 444 (46%) of 965 had unlikely tuberculosis, 282 (29%) had unconfirmed tuberculosis, and 239 (25%) had confirmed tuberculosis. Median age was 5·0 years (IQR 1·8–9·0); 467 (48%) of 965 children were female and 498 (52%) were male. 155 (16%) of 965 children had HIV and 110 (11%) children had SAM. 196 (82%) of 239 children with microbiological detection tested positive on Ultra. 110 (46%) of 239 were confirmed by both Ultra and culture, 86 (36%) by Ultra alone, and 43 (18%) by culture alone. ‘Trace’ was the most common semiquantitative result (93 [40%] of 234). 481 (50%) of 965 children had only one specimen type collected, 99 (21%) of whom had M tuberculosis detected. 484 (50%) of 965 children had multiple specimens collected, 141 (29%) of whom were positive on at least one specimen type. Of the 102 children younger than 5 years with M tuberculosis detected, 80 (78%) tested positive on sputum. 64 (80%) of 80 children who tested positive on sputum were positive on sputum alone; 61 (95%) of 64 were positive on induced sputum, two (3%) of 64 were positive on spontaneous sputum, and one (2%) was positive on both. High rates of microbiological confirmation of tuberculosis in children can be achieved via parallel sampling and concurrent testing procedures. Sample types and choice of test to be used sequentially should be considered when applying to groups such as children younger than 5 years, living with HIV, or with SAM. European and Developing Countries Clinical Trials Partnership programme, supported by the EU, the UK Medical Research Council, Swedish International Development Cooperation Agency, Bundesministerium für Bildung und Forschung, the German Center for Infection Research, and Beckman Coulter.

Alternative tools are needed to improve the detection of M. tuberculosis (M. tb) in HIV co-infections. We evaluated the utility of Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) compared to lipoarabinomannan (LAM) to detect M. tb in urine. Sputum Xpert MTB/RIF-positive patients were consented to provide urine at baseline, weeks 2, 8, 16, and 24 of treatment for TB-MBLA, culture, and LAM. Results were compared with sputum cultures and microscopy. Initial M. tb. H37Rv spiking experiments were performed to validate the tests. A total of 63 urine samples from 47 patients were analyzed. The median age (IQR) was 38 (30–41) years; 25 (53.2%) were male, 3 (6.5%) had urine for all visits, 45 (95.7%) were HIV positive, of whom 18 (40%) had CD4 cell counts below 200 cells/µL, and 33 (73.3%) were on ART at enrollment. Overall urine LAM positivity was 14.3% compared to 4.8% with TB-MBLA. Culture and microscopy of their sputum counterparts were positive in 20.6% and 12.7% of patients, respectively. Of the three patients with urine and sputum at baseline, one (33.33%) had urine TB-MBLA and LAM positive compared to 100% with sputum MGIT culture positive. Spearman’s rank correction coefficient (r) between TB-MBLA and MGIT was −0.85 and 0.89 with a solid culture, p > 0.05. TB-MBLA has the promising potential to improve M. tb detection in urine of HIV-co-infected patients and complement current TB diagnostics.

Digital health interventions, such as electronic immunization registries (eIRs) and electronic logistic management information systems (eLMIS), have the potential to significantly improve immunization data management and vaccine logistics in low- and middle-income countries (LMICs). Despite their growing adoption, there is limited evidence of the financial and economic costs associated with their implementation compared to traditional paper-based systems. We aimed to measure the costs of implementing eIR and eLMIS systems in LMICs and to estimate their economic costs as compared to the previous paper-based registries. The study was conducted across four countries-Guinea, Honduras, Rwanda, and Tanzania-which implemented the tools in 2018, 2012, 2019, and 2014, respectively. A combination of primary and secondary data sources was used for the analysis. Retrospective cost data regarding the design, development, and implementation of the tools were directly obtained from implementers and National Immunization Program offices in all countries. Primary survey data were collected to gauge the operational expenses of immunization information systems, both with and without electronic tools, using an activity-based costing approach in 275 facilities. The annual cost of the immunization information system at the national level was then extrapolated and compared to national spending on immunization as a measure of affordability. Costs were reported in 2023 international dollars (I$). The total costs of designing, developing, and deploying eIR, eLMIS, or both were I$ 2.2, 6.4, 6.8, and 44.3 million in Guinea, Honduras, Rwanda, and Tanzania, respectively. Design costs were greatly affected by the degree of customization of the tool, whereas rollout costs were mostly driven by the costs of purchasing hardware and training health workers. Overall, the implementation of the electronic systems was associated with higher costs in Honduras (I$626 per facility, 95% CI 516-821) and Rwanda (I$399, 95% CI I$108-I$691), a cost reduction in Tanzania (-I$2539, 95% CI -I$4290 to -I$789) and no significant cost difference in Guinea. The percentage weight of the cost of managing data with the electronic systems over the total national immunization budgets was estimated at 0.7%, 7.7%, 3.3%, and 4.8% for Guinea, Honduras, Rwanda, and Tanzania, respectively. Digital health interventions such as eIR and eLMIS can potentially reduce costs and improve the efficiency of immunization data management and vaccine logistics in LMICs. However, the extent of cost savings depends on how effectively these digital systems replace traditional paper-based methods and the extent of their use in decision-making, especially at the facility level. Careful planning and investment are essential to unlocking the full economic potential of digital health in LMICs.

Background Tuberculosis (TB) symptom screening and testing using either smear microscopy or GeneXpert MTB/RIF Ultra (Xpert Ultra) have been the mainstay for diagnosing TB disease in case finding. Reliance on symptom-based TB screening results in missed TB cases, and universal TB testing approach might be more suitable to find missing TB cases in high-risk populations. Universal TB testing involves testing for TB disease regardless of TB symptoms in those at risk of TB. However, limited evidence exists to support its adoption including cost-effectiveness. In this study, we will evaluate the effectiveness of universal TB testing for detection of TB and uptake of TB preventive therapy (TPT) among eligible household and community contacts in high TB settings as per country guidelines. Methods This is a pragmatic cluster-randomised trial conducted in Lesotho and Tanzania. Drug-sensitive TB (DS-TB) index patients aged ≥ 18 years, who have at least one contact, will be enrolled if they are microbiologically confirmed with TB within ≤ 6 weeks of diagnosis at the time of recruitment by study team at health facilities in selected districts or regions. Each TB index patient and their contact(s) will be randomised into either universal TB testing or standard TB screening arms. Household and community contacts listed by each TB index case will be enumerated and invited to participate in the study after providing informed consent or assent during household visits. The study has four sub-studies including health economics and modelling, paediatrics, microbiology, and socio-behavioural. A preparatory cross-sectional study will be conducted before delivery of the pragmatic cluster-randomised trial. It will determine the prevalence of TB infection (TBI), TPT eligibility in household contacts (HHCs), and compare the performance of QuantiFERON-TB-Gold-Plus (QFT-Plus) and QIAreach for diagnosing TBI among HHCs of TB index patients. Cluster-randomised trial and community contact tracing will be conducted in phase II. Significance This trial will provide evidence for a more intensive approach which is hypothesised to increase cost-effectiveness of TB case finding. In addition, it will provide evidence for high TB burden countries with inherently different cost structures compared to intermediate and low burden settings where previous cost-effectiveness analyses have been undertaken. Clinical trial registration number BMC Trial Registry ISRCTN10003903. Registered on December 22, 2020. Protocol version number and date. Version 1.2, dated 15 January 2023. Date recruitment began. 1 March 2022. Estimated date of recruitment completion. 31 July 2025.

ObjectiveTo describe challenges posed by COVID-19 on tuberculosis (TB) commodity supply, care cascade, active case finding and responses taken by healthcare workers (HCWs) and community health workers (CHWs) during the first year of the pandemic (March 2020 to February 2021).DesignA qualitative descriptive study involving 25 in-depth interviews and 10 focus group discussions conducted in July 2022.Setting37 TB treatment facilities were purposively selected from seven regions due to high TB case notifications in 2019 and their provision of TB and COVID-19 services during the first year of the pandemic (March 2020 to February 2021).ParticipantsPurposive selection of 58 HCWs and 55 CHWs who provided TB services in the first year of the COVID-19 pandemic.ResultsHCWs reported unusual stockouts and delayed receipt of GeneXpert cartridges and sputum containers. TB services faced a decline in client attendance, as clients were hesitant to undergo TB screening, sputum sample collection and contact tracing due to fear of contracting or being diagnosed with COVID-19 and subsequently being quarantined. To mitigate these challenges, HCWs used alternative containers for sputum sample collection, optimised GeneXpert cartridge use by prioritising GeneXpert testing for TB risk groups and diagnosed TB by microscopy, chest X-ray and sputum pooling method. Moreover, they extended drug refill schedules to minimise the risk of contracting COVID-19 in clinics. CHWs used mobile communication for client tracing and focused household visits on TB risk groups.ConclusionCOVID-19 disrupted TB commodity availability and TB treatment-seeking behaviour. Adaptations like multi-month drug refills and optimised GeneXpert use supported the TB healthcare system’s resilience. While these adaptations offer valuable insights for strengthening TB service delivery, their effectiveness and sustainability require further evaluation. Thus, prospective studies could clarify their long-term impact. National Tuberculosis Program could consider adapting these practices postpandemic, with appropriate modifications to suit different contexts.